Applicants claim the benefit of the earlier filing date of Great Britain Application No. 9930519.5, filed Dec. 24, 1999, which is incorporated herein by reference in its entirety.
This invention relates to uses of transport-active proteins, particularly of proteins and fusion polypeptides with the function of VP22, for control of the cell cycle, particularly in the reduction of the proliferating activity of proliferating cells.
The transport properties of VP22 and homologues thereof are described in WO 97/05265 (P O""Hare and G Elliott). WO 98/32866 (P O""Hare et al.) discusses coupled polypeptides and fusion polypeptides for intracellular transport, and their preparation and use. Intercellular trafficking and protein delivery by a herpesvirus structural protein is described in Cell (1997), Vol. 88, pp223-233 (G Elliott and P O""Hare).
The prior art generally includes a variety of cell cycle control proteins, especially in the forms of protein and polynucleotide sequences enabling genetic manipulation by standard techniques.
For example, among cell cycle control proteins, protein p53 is known as a tumor suppressor. p53 is a 53 kDa nuclear phosphoprotein. Wild type and mutant p53 proteins have been expressed by means of recombinant vaccinia viruses (Ronen et al., Nucleic Acids Research, 20, pp 3435-3441, 1992). p53 functions to regulate cell cycle progression and under conditions of DNA damage can induce cell cycle arrest or apoptosis through a complex signal transduction mechanism (Levine A. J. Cell, 88, pp323-331, 1997).
Other proteins known to promote cell death include the bax protein, and homologues such as the Bak protein, including its BH3 domain (E P Hollinger et al., 1999, J Biol. Chem., 274 (19), pp 13298-13304).